Our overall objective is to provide safe, effective, practical family-centered and integrated prevention, treatment and cure for HIV, TB and other comorbidities in individuals of all races, ages and gender, continuously refined through quality research, innovation and implementation. HIV/AIDS and TB are major global public health problems. South Africa has the highest population prevalence of HIV infection globally and the highest incidence in the world, with >60% of TB cases also HIV-infected. The SUN-CTU is located at the Faculty of Medicine and Health Sciences in urban Cape Town, Western Cape Province of South Africa, an epicenter of these twin epidemics, serving a population of approximately 2.5 million. SUN-CTU combines excellence in research and clinical care with a high prevalence of HIV and TB and populations accessed through 3 closely linked Clinical Research Sites (CRSs) with complementary research focus, strategically situated satellites and proven capacity for a broad spectrum of research. SUN-CTU has a strong family-centered approach, focusing on HIV- and TB-related research and care to large at-risk populations, spanning low birth weight and premature neonates, infants, children, adolescents and adults of all ages. The proposed well-integrated SUN-CTU is a pluripotent network expansion of an existing smaller CTU, at the Children's Infectious Diseases Clinical Research Unit (KID-CRU), focused on IMPAACT network activities. SUN-CTU has already demonstrated considerable capacity to conduct multiple clinical research projects through NIAID and other funding sources, and is particularly well aligned for participation in the IMPAACT, ACTG and HPTN networks.